The Niche

Notes on a neural stem cell conference

Editor’s note: The stem cell world has been rich with conferences in the past week or so. I hope to have very brief notes on Cold Spring Harbor Laboratory and Stanford’s interdisciplinary program on stem cell policy over the next few days. For the recent World Stem Cell Conference in Baltimore, please check for Elie Dolgin’s posts in In the Field.

The conference report below comes from Julie Clark, a scientist at Stemgent, who had previously covered the ISSCR conference for the Niche, and volunteered again. Thanks very much to Julie! —Monya

UCSF began October with its 2nd International Stem Cell Symposium: Frontiers in Neural Stem Cells . The planning committee brought together 23 of the leading authorities in neuroscience and made available a real-time symposium blog (http://nscmeeting.blogspot.com/) to facilitate Q&A.

With the possibility of cell replacement therapy on the horizon, this symposium probed how neural stem cells function in brain development and repair.

The origin of neural stem cells and building and repairing the cortex were the emphasis of the first of this two day symposium. Here are a few highlights.


Fingering zinc in cell fate

Yoshiki Sasai, MD, PhD from Kobe RIKEN discussed the identification of Zfp521, a zinc finger protein required for the transition of common ectoderm cells to a neuroectodermal fate. Sasai showed the forced up-regulation of Zfp521 causes neural differentiation and its knock down inhibits neural differentiation of embryonic stem cells.

Susan McConnell PhD from Stanford identified another zinc finger protein, Fezf2, which appears to regulate motor neuron fate. Loss of Fezf2 results in the failure of neurons to send axons to the spinal cord and development of the corpus callosum.

New sorts of neural stem cells

Arnold Kriegstein MD, PhD from UCSF wowed the crowd with videos of radial glial cell (RGC) division, showing that during cell division RGCs do not retract their axons. Once thought to be just scaffolding, radial glial cells have been shown to be NSCs/progenitors.

Derek van der Kooy, PhD from the University of Toronto showed evidence that a small population of leukemia inhibitory factor (LIF) sensitive primitive neural stem cells (NSCs) is preserved in the adult forebrain (approximately 5-10 cells in adult mice). Primitive NSCs can be activated to replace the definitive neural stem cells lost to chemical stress.

The eyes have it

Sally Temple PhD from the New York Stem Cell Institute showed that cells of the retinal pigment epithelium (RPE)collected from the sub-retinal fluid discarded after retinal surgeries can be isolated from human eye, expanded, and differentiated into a variety of cells (e.g. retinal cells, neurons, fat, chondrocytes, and bone). RPE cell biopsies would require putting needles into the sub-retinal space, a very routine procedure for retinal surgeons and can be considered as a source of patient matched progenitor cells for regenerative medicine.

Meninges push proliferation

Samuel Pleasure MD, PhD discussed the role of the meninges in cortical neurogenesis. In addition to functioning as the basement membrane for radial glia attachment, Pleasure showed that the cortical meninges also secret soluble factors (e.g. retinoic acid), influencing the transition of symmetrical to asymmetrical phase proliferation of neural stem cells crucial to the production of neurons in the underlying cortex.

Day2

The second day of the International Stem Cell Symposium: Frontiers in Neural Stem Cells had an equally impressive lineup of speakers with surprisingly passionate requests for scientific diversity and support for basic research funding. The emphases of the second day were on generating new neurons and glial cells and stem cell models of neurological disease.

Pheromones, neurons make social memories; social changes change neuron survival

Samuel Weiss PhD from the University of Calgary showed evidence of adult neurogenesis in response to pheromones resulting in the formation of social memories (e.g. recognition of offspring) in mice.

Fernando Nottebohm PhD from Rockerfeller University discussed the effects on neuron survival or killing as a result of social changes in zebra finches. Nottebohm also reflected on the changing belief of adult neurogenesis during his scientific career, spanning over 4 decades, but will be remembered most for his passionate plea advocating that governments and young scientists move toward basic science and resist the push for translational research “studies of aging are studies of boredom.”

Competition at the synapse

Fred Gage PhD from the Salk Institute showed that neural synapses are maintained through competition between new and old neurons and new neurons add complexity to pattern separation and integration. Gage further showed retrotransposons line elements creating genetic mosaics in the brain.

Astrocytes instigate synapses

Ben Barres MD, PhD from Stanford presented data from a soon to be published manuscript in Cell, showing that thrombospondin, a soluble factor released by astrocytes, induces an increase in synapse number on retinal ganglion cells by binding to the calcium channel subunit α2δ. The calcium channel subunit α2δ is also the receptor for gabapentin and pregabalin drugs currently used for the treatment of pain and epilepsy. Barres also took some time to reflect on the dearth of women in science asking everyone to view his talk on the matter of diversity in science which can be found at the following link (www.memdir.org/video/barres.html) and encouraging “students to come out as gays and women to come out as women as well.”

Human glial progenitors myelinate, move in on mouse brain

Steven Goldman MD, PhD from the University of Rochester used human glial progenitor cells from 23 week old medically necessary aborted fetal brains to treat a mouse model of myelin disease. Human progenitor cells were able to differentiate in a context dependent manner, remyelinate, and rescue the disease phenotype. Surprisingly Goldman found that over time (approximately 13 months) the human progenitor cells took over and replaced all neural cells in the mouse brain creating a humanized-mouse brain model system. This study is currently in press at Cell Stem Cell.

Small molecules push fibroblasts toward ES cell morphology

The symposium ended with Kevin Eggan PhD from Harvard University who presented his work on finding small molecule inducers of reprogramming resulting in compounds repsox and repoct. Although the combination of these two compounds could not FULLY reprogram cells, their combination did prompt fibroblast cells to form colonies resembling those of embryonic stem cells, albeit they did not express Oct4.

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